Deletion of dopamine D 2 receptors from parvalbumin interneurons in mouse causes schizophrenia-like phenotypes

Significance Schizophrenia and bipolar disorder are psychiatric syndromes with a significant social and economic burden that share a common symptom, psychosis, attributed to excessive dopamine release. Despite years of intensive research, the causes of these devastating diseases are still unknown. In this work, a mouse line with a selective deletion of the molecular target of antipsychotics, dopamine D 2 receptors, from the most affected neuron subtype in patients, parvalbumin interneurons, results in animals with schizophrenia-like phenotypes and resistance to the broadly used antipsychotic aripiprazole. Therefore, this genetic dissection provides clues about the intrinsic molecular mechanism leading to a dysregulated dopamine system and the development of psychiatric conditions like schizophrenia, bringing opportunities to develop diagnostic and treatment approaches.